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1.
Prev Med Rep ; 47: 102886, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39351277

RESUMO

This study was conducted from June to September 2020 and conducted a population-based study of 2149 rural Dai residents aged 50 years or above in Xishuangbanna. The definition of hypertension was a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, or a current treatment plan with an antihypertensive medication. High blood pressure (HBP) included the following subtypes: SDH, ISH and IDH. All participants were interviewed, had physical examinations performed, and had blood pressure measurements taken. Multivariable logistic regression analysis was applied to analyse the risk factors for hypertension. The prevalence of HBP was 43.2 %. The subtype-specific prevalence of hypertension was 16.5 % for SDH, 24.2 % for ISH and 2.5 % for IDH. Among hypertensive participants, 38.2 % were SDH, 56.0 % were ISH and 5.8 % were IDH. Older age is a risk factor for HBP and ISH. Obesity, smoking, drinking and history of hypertension are risk factors for HBP and its subtypes including SDH and ISH (OR >1). Among all the hypertensive participants, only 25.0 % of the participants were aware of their hypertension while 34.7 % of SDH participants, 20.0 % of ISH participants and 9.3 % of IDH participants knew the individual subtype of hypertension. Among Dai people, the prevalence of hypertension is high, while the awareness and the rate of adequate treatment of hypertension is low. ISH stood out as the most prevalent type of HBP among the rural elderly. Rising ageing population in China, ISH remains an important public health problem and a challenging management issue in rural China.

2.
Rev Cardiovasc Med ; 25(8): 277, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39228479

RESUMO

Acute coronary syndrome (ACS) poses a significant threat to health and well-being, although percutaneous coronary intervention (PCI) is an effective treatment method. However, many patients undergoing PCI for coronary heart disease often experience negative emotions such as depression and anxiety, as well as sleep disturbances, poor adherence to medications, and somatic symptoms. These adverse psychological effects can contribute to an increased risk of cardiovascular events. Mindfulness-based stress reduction (MBSR), a highly effective mind-body therapy, has been increasingly utilized in the recovery process of patients with coronary heart disease. Several scholars have conducted mindfulness interventions for post-PCI patients with coronary heart disease and achieved promising outcomes. This article primarily focuses on applying mindfulness-based stress reduction in PCI patients with coronary heart disease and its future prospects.

3.
J Hazard Mater ; 480: 135883, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39303617

RESUMO

Microbial remediation of heavy metal (HM)-contaminated soil is a sustainable approach; however, the impact of microbial inoculation on the internal environment of plants remains understudied. Thus, Enterobacter sp. FM-1 (Enterobacter sp.) and the hyperaccumulator Bidens pilosa L. (B. pilosa L.) were used to study these effects. Through analyses of plant physiological and biochemical characteristics, the endophytic microbial community composition, microbial co-occurrence networks and functional predictions, the potential mechanisms by which Enterobacter sp. benefits the phytoremediation of HM-contaminated soil by B. pilosa L. were elucidated. Inoculation with Enterobacter sp. promoted the growth of B. pilosa L. and influenced the endophytic microbial community diversity in B. pilosa L. Interactions among endophytes facilitated the formation of microbial networks, with endophytic fungi playing a more prominent role than endophytic bacteria as the level of HM contamination increased. Functional predictions via PICRUSt2 revealed that endophytic bacteria are involved primarily in processes related to carbohydrate metabolism, ABC transporters, and amino acid metabolism. In conclusion, this study provides evidence for the beneficial role of microbes in improving the plant endosphere environment.

4.
Digit Health ; 10: 20552076241277027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193314

RESUMO

Objective: Explainable machine learning (XAI) was introduced in this study to improve the interpretability, explainability and transparency of the modelling results. The survex package in R was used to interpret and compare two survival models - the Cox proportional hazards regression (coxph) model and the random survival forest (rfsrc) model - and to estimate overall survival (OS) and its determinants in heart failure (HF) patients using these models. Methods: We selected 1159 HF patients hospitalised at the First Affiliated Hospital of Kunming Medical University. First, the performance of the two models was investigated using the C-index, the integrated C/D AUC, and the integrated Brier score. Second, a global explanation of the whole cohort was carried out using the time-dependent variable importance and the partial dependence survival profile. Finally, the SurvSHAP(t) and SurvLIME plots and the ceteris paribus survival profile were used to obtain a local explanation for each patient. Results: By comparing the C-index, the C/D AUC, and the Brier score, this study showed that the model performance of rfsrc was better than coxph. The global explanation of the whole cohort suggests that the C-reactive protein, lg BNP (brain natriuretic peptide), estimated glomerular filtration rate, albumin, age and blood chloride were significant unfavourable predictors of OS in HF patients in both the cxoph and the rfsrc models. By including individual patients in the model, we can provide a local explanation for each patient, which guides the clinician in individualising the patient's treatment. Conclusion: By comparison, we conclude that the model performance of rfsrc is better than that of coxph. These two predictive models, which address not only the whole population but also selected patients, can help clinicians personalise the treatment of each HF patient according to his or her specific situation.

5.
Nature ; 631(8021): 531-536, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39020034

RESUMO

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.

6.
Heart Vessels ; 39(7): 605-615, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38502317

RESUMO

BACKGROUND: The prognostic nutritional index (PNI) and serum chloride level are related to adverse outcomes in patients with heart failure. However, little is known about the relationship between the PNI and serum chloride level in predicting the poor prognosis of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We reviewed 1221 consecutive patients with ADHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in hospital death, missing follow-up data, missing chloride data, missing lymphocyte (LYM) count data, or missing serum albumin data, 805 patients were included. PNI was calculated using the formula: serum albumin (ALB) (g/L) + 5 × LYM count (10^9/L). Patients were divided into 4 groups according to the quartiles of the PNI, and the highest PNI quartile (PNI Q4: PNI ≥ 47.3) was set as the reference group. The patients in the lowest PNI quartile (PNI Q1: PNI < 40.8) had the lowest cumulative survival rate, and mortality risk decreased progressively through the quartiles (log-rank χ2 142.283, P < 0.0001). Patients with ADHF were divided into 8 groups by quartiles of PNI and median levels of serum chloride. After adjustment, the hazard ratio (HR) for all-cause mortality in ADHF patients in Group 1 was 8.7 times higher than that in the reference Group 8. Furthermore, the addition of serum chloride level and PNI quartile to the Cox model increased the area under the Receiver operating characteristic (ROC) curve by 0.05, and the area under the ROC curve of the new model was higher than that of the original model with traditional risk factors. CONCLUSIONS: Both the lowest PNI quartiles and low chloride level indicate a higher risk of all-cause death in patients with ADHF.


Assuntos
Biomarcadores , Cloretos , Insuficiência Cardíaca , Avaliação Nutricional , Humanos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Prognóstico , Cloretos/sangue , Idoso , Estudos Retrospectivos , Doença Aguda , Biomarcadores/sangue , Valor Preditivo dos Testes , Medição de Risco/métodos , Pessoa de Meia-Idade , China/epidemiologia , Fatores de Risco , Curva ROC , Taxa de Sobrevida/tendências , Estado Nutricional , Idoso de 80 Anos ou mais , Seguimentos
7.
Libyan J Med ; 19(1): 2309757, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38290043

RESUMO

The ratio of fibrinogen to albumin (FAR) is considered a new inflammatory biomarker and a predictor of cardiovascular disease risk. However, its prognostic value for patients with chronic heart failure (CHF) with different ejection fractions (EFs) remains unclear. A total of 916 hospitalized patients with CHF from January 2017 to October 2021 in the First Affiliated Hospital of Kunming Medical University were included in the study. Death occurred in 417 (45.5%) patients out of 916 patients during a median follow-up time of 750 days. Among these patients, 381 patients suffered from HFrEF (LVEF <40%) and 535 patients suffered from HFpEF or HFmrEF (HFpEF plus HFmrEF, LVEF ≥ 40%). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR (9.06) obtained from receiver operating characteristic (ROC) curve analysis. Upon analysing the Kaplan - Meier plots, the incidence of death was significantly higher in all patients with FAR-H and patients in both HF subgroups (p < 0.001). The multivariate Cox proportional hazard analyses indicated that the FAR was an independent predictor of all-cause mortality, regardless of heart failure subtype. (HR 1.115, 95% CI 1.089-1.142, p < 0.001; HFpEF plus HFmrEF, HR 1.109, 95% CI 1.074-1.146, p < 0.0001; HFrEF, HR 1.138, 95% CI 1.094-1.183, p < 0.0001) The optimal cut-off value of FAR in predicting all-cause mortality was 9.06 with an area under the curve value of 0.720 (95% CI: 0.687-0.753, p < 0.001), a sensitivity of 68.8% and a specificity of 65.6%. After adjusting for the traditional indicators (LVEF, Lg BNP, etc.), the new model with the FAR had better prediction ability in patients with CHF. Elevated FAR is an independent predictor of death in CHF and is not related to the HF subtype.


Assuntos
Insuficiência Cardíaca , Humanos , Prognóstico , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Incidência
8.
Cardiology ; 149(3): 237-247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38262371

RESUMO

INTRODUCTION: The prognostic value of the ratio of haemoglobin to red cell distribution width (HRR) in different types of heart failure (HF) is not well known. METHOD AND RESULTS: We analysed the long-term prognostic value of HRR in patients with HF using the Cox proportional risk model and Kaplan-Meier method. We reviewed consecutive 972 HF patients. The overall mortality rate was 45.68%. Mortality was 52.22% in the HFrEF group and 40.99% in the HFpEF + HFmrEF group. Cox regression showed that when HRR increased by 1 unit, the risk of all-cause death in all HF patients decreased by 22.8% (HR: 0.772, 95% CI: 0.724, 0.823, p < 0.001), in the HFpEF + HFmrEF group it decreased by 15.5% (HR: 0.845, 95% CI: 0.774, 0.923, p < 0.001), and in the HFrEF group it decreased by 36.1% (HR: 0.639, 95% CI: 0.576, 0.709, p < 0.0001). Subgroup analysis showed that there were interactions between the EF and HRR groups. The group in which HRR best predicted all-cause death from HF was group 1 (EF <40%, HRR <9.45), followed by group 2 (EF <40%, HRR ≥9.45), and group 3 (EF ≥40%, HRR <9.45). HRR had no predictive value in group 4 (EF ≥40%, HRR ≥9.45). CONCLUSION: HRR is an important predictor of all-cause mortality in patients with HF, especially HFrEF. There is an interaction between HRR group and LVEF group.


Assuntos
Índices de Eritrócitos , Insuficiência Cardíaca , Hemoglobinas , Volume Sistólico , Humanos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Hemoglobinas/análise , Prognóstico , Modelos de Riscos Proporcionais , Valor Preditivo dos Testes , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Causas de Morte , Idoso de 80 Anos ou mais
9.
Cardiovasc Toxicol ; 24(2): 133-145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38180639

RESUMO

Cardiac Vascular disease particularly myocardial infarction (MI) is a threat to health worldwide. microRNAs (miRNAs) have been shown to regulate myocardial fibrosis. Therefore, it is potential to investigate the mechanism of miRNA and fibrosis following myocardial infarction. Hypoxia human cardiac microvascular endothelial cells (HCMECs) were selected for the vitro experimental model. The miR-146a-5p expression was tested via RT-qPCR. The level of endothelial-to-mesenchymal transition (EndMT) and fibrosis markers were detected by Western blotting and immunofluorescence. Then, the inflammation, cell viability and apoptosis were investigated. The target was predicted by an online database and verified by a dual-luciferase activity assay. An MI mouse model was created to validate that miR-146a-5p regulates cardiac fibrosis in vivo. MI mouse was transfected with miR-146a-5p lentivirus. Subsequently, its effect on cardiac fibrosis of infarcted hearts was assessed by In situ hybridization (ISH), Immunohistochemistry (IHC), Triphenylterazolium chloride (TTC) staining and Masson staining. Herein, we confirmed that miR-146a-5p was down-regulated in hypoxia HCMECs. Overexpression of miR-146a-5p inhibited hypoxia-induced cardiac fibrosis following myocardial infarction by inhibiting EndMT in HCMECs. Thioredoxin-interacting protein (TXNIP) was a target that was negatively regulated by miR-146a-5p. Up-regulation of miR-146a-5p inhibited cardiac fibrosis via regulating EndMT by targeting TXNIP, and it also regulated EndMT to inhibit cardiac fibrosis in vivo.


Assuntos
Cardiomiopatias , MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Camundongos , Apoptose , Cardiomiopatias/metabolismo , Células Endoteliais , Transição Endotélio-Mesênquima , Fibrose , Hipóxia/complicações , Hipóxia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/metabolismo
10.
BMC Cardiovasc Disord ; 24(1): 54, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233747

RESUMO

OBJECTION: Inflammatory conditions and immune disorders may worsen the prognosis of chronic heart failure (CHF) patients. The aim of this study was to evaluate the prognostic value of a new indicator, C-NLR, composed of C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), for the risk of all-cause mortality in HF patients with different ejection fractions. METHODS: A total of 1221 CHF patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021 were enrolled in this study. All patients were divided into 2 groups according to the median C-NLR. Kaplan-Meier survival curves were used to compare the all-cause mortality among CHF patients with different ejection fractions. Cox proportional hazards analysis was used to evaluate the relationships between variables and mortality. The predictive value of the C-NLR was assessed by using receiver operating characteristic (ROC) analyses. RESULTS: We collected data from 1192 patients with CHF. Kaplan-Meier survival analysis revealed that patients with low LCR levels had better overall survival (OS). After multivariate adjustment Cox proportional hazards analysis, the level of C-NLR was still independently related to mortality. CONCLUSIONS: C-NLR was a competent independent predictor in HF with different ejection fractions, and routine measurement of C-NLR would help clinical doctors identify patients with a poor prognosis.


Assuntos
Insuficiência Cardíaca , Neutrófilos , Humanos , Neutrófilos/metabolismo , Prognóstico , Estudos Retrospectivos , Linfócitos/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo
11.
BMC Med Inform Decis Mak ; 23(1): 267, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985996

RESUMO

BACKGROUND: The goal of this study was to assess the effectiveness of machine learning models and create an interpretable machine learning model that adequately explained 3-year all-cause mortality in patients with chronic heart failure. METHODS: The data in this paper were selected from patients with chronic heart failure who were hospitalized at the First Affiliated Hospital of Kunming Medical University, from 2017 to 2019 with cardiac function class III-IV. The dataset was explored using six different machine learning models, including logistic regression, naive Bayes, random forest classifier, extreme gradient boost, K-nearest neighbor, and decision tree. Finally, interpretable methods based on machine learning, such as SHAP value, permutation importance, and partial dependence plots, were used to estimate the 3-year all-cause mortality risk and produce individual interpretations of the model's conclusions. RESULT: In this paper, random forest was identified as the optimal aools lgorithm for this dataset. We also incorporated relevant machine learning interpretable tand techniques to improve disease prognosis, including permutation importance, PDP plots and SHAP values for analysis. From this study, we can see that the number of hospitalizations, age, glomerular filtration rate, BNP, NYHA cardiac function classification, lymphocyte absolute value, serum albumin, hemoglobin, total cholesterol, pulmonary artery systolic pressure and so on were important for providing an optimal risk assessment and were important predictive factors of chronic heart failure. CONCLUSION: The machine learning-based cardiovascular risk models could be used to accurately assess and stratify the 3-year risk of all-cause mortality among CHF patients. Machine learning in combination with permutation importance, PDP plots, and the SHAP value could offer a clear explanation of individual risk prediction and give doctors an intuitive knowledge of the functions of important model components.


Assuntos
Insuficiência Cardíaca , Humanos , Teorema de Bayes , Doença Crônica , Análise por Conglomerados , Aprendizado de Máquina
12.
BMC Cardiovasc Disord ; 23(1): 565, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978441

RESUMO

BACKGROUND: This study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into four groups, according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r = 0.348, p < 0.001) and no interaction (p = 0.140) between the ALI and GNRI. Kaplan‒Meier analysis showed that the cumulative incidence of all-cause mortality in patients with HF was highest in Group 1 (log-rank χ2 126.244, p < 0.001). Multivariate Cox proportional hazards analysis revealed that ALI and GNRI were independent predictors of all-cause mortality in HF patients (ALI: HR 0.407, 95% CI 0.296-0.560, p < 0.001; GNRI: HR 0.967, 95% CI 0.954-0.980, p < 0.001). The area under the curve (AUC) for ALI combined with GNRI was 0.711 (p < 0.001), according to the time-dependent ROC curve. CONCLUSION: ALI and GNRI were independent predictors of all-cause mortality in HF patients. Patients with HF had the highest risk of all-cause mortality when the ALI was < 24.60 and the GNRI was < 94.41. ALI combined with the GNRI has good predictive value for the prognosis of HF patients.


Assuntos
Insuficiência Cardíaca , Neoplasias Pulmonares , Humanos , Idoso , Avaliação Nutricional , Neoplasias Pulmonares/diagnóstico , Insuficiência Cardíaca/diagnóstico , Prognóstico , Inflamação/diagnóstico , Estado Nutricional , Fatores de Risco , Estudos Retrospectivos
13.
Biomed Pharmacother ; 165: 115114, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37467649

RESUMO

Bifunctional chelators (BFCs), which link metallic radionuclide and a targeting vector, are some of the most crucial components of metallic radionuclide-based radiopharmaceuticals for positron-emission computed tomography (PET) imaging. In this study, we designed and synthesized two versatile BFCs, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA, and we conjugated them with a prostate-specific membrane antigen (PSMA) inhibitor. These two chelators showed high affinity for Ga (III) according to a study of the thermodynamics and kinetics and DFT calculations. The labeled PSMA targeted probes, [68Ga]Ga-p-NCS-Ph-DE4TA-PSMA and [68Ga]Ga-p-NCS-Ph-AAZ4TA-PSMA, maintained excellent stability in vitro, and they exhibited high specific activity when binding to PSMA. A PET/CT imaging study in mice bearing SMMC-7721 hepatocellular carcinoma xenografts demonstrated clear visualization of tumors with a high tumor uptake and low background level, indicating the excellent performance in vivo and specific activity when targeting hepatocellular carcinomas. In summary, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA are leading developmental candidates for PET imaging for tumor diagnosis.


Assuntos
Peptidomiméticos , Neoplasias da Próstata , Masculino , Humanos , Animais , Camundongos , Compostos Radiofarmacêuticos/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Quelantes , Radioisótopos , Tomografia por Emissão de Pósitrons/métodos , Termodinâmica , Linhagem Celular Tumoral
14.
Int Heart J ; 64(4): 700-707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37518352

RESUMO

Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF) with different ejection fractions. We sought to determine the postdischarge outcomes associated with lower serum chloride between different CHF types.We reviewed the medical records of 1221 consecutive patients with CHF admitted to the First Affiliated Hospital of Kunming Medical University from January 2017 to October 2021. After excluding patients with in-hospital death, missing follow-up data, missing serum chloride level data, or chronic dialysis therapy, 791 patients were included. Of these patients, 343 had heart failure with reduced ejection fraction (HFrEF; i.e., left ventricular ejection fraction (LVEF) < 40%), and 448 had heart failure with preserved ejection fraction (HFpEF) or heart failure with median ejection fraction (HFmrEF; HFpEF plus HFmrEF; i.e., LVEF ≥40%). Over a median follow-up of 750 days, 344 patients (43.5%) had all-cause mortality. In the univariate analysis, serum sodium and chloride were strongly associated with mortality in both HF subgroups (P < 0.0001). A multivariable model including both serum sodium and chloride showed the highly significant association between serum chloride and survival (P < 0.0001), whereas the association between serum sodium and mortality was not reported (HFpEF plus HFmrEF, hazard ratio (HR) 0.975, 95% confidence interval [CI] 0.942-1.010, P = 0.158; HFrEF, HR 1.007, 95% CI 0.966-1.051, P = 0.734). Kaplan-Meier survival curve analysis revealed a significant difference in mortality risk with decreasing chloride levels in all patients with CHF. The optimal cutoff value of chloride in predicting all-cause mortality was 102.95 mmol/L with area under the curve value of 0.76 [HR 0.760, 95% CI 0.727-0.793, P < 0.0001], sensitivity of 60.2%, and specificity of 78.3%.Lower serum chloride is an independent predictor of death in CHF, regardless of heart failure subtype.

15.
Mikrochim Acta ; 190(5): 167, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37012478

RESUMO

A hairpin DNA-enabled ratiometric electrochemical aptasensor is reported for sensitive and reliable detection of malathion (MAL). The approach employs hairpin DNA (ferrocene-labeled, Fc-hDNA) as a carrier to hybridize MAL aptamers (methylene blue-labeled, MB-Apt) to form double-stranded DNA structures on an electrode. The presence of MAL induces the removal of aptamers, and hDNA re-forms hairpin structures, causing a decrease in the oxidation current of MB (IMB) and an increase in the oxidation current of Fc (IFc). The ratiometric signal of IFc/IMB responds quantitatively to MAL concentrations. To compare analytical performances, a linear single-stranded DNA (ssDNA) is also used to construct the ssDNA-based aptasensor. We demonstrate that hairpin DNA possessing a rigid two-dimensional structure can improve the assembly efficiency of aptamers and the stability of redox probes. The approach combines the advantages of the ratiometric electrochemical method with hairpin DNA-based conformational switching probes, enabling hDNA-based aptasensor with enhanced sensitivity and reliability, offering a linear range of 0.001 to 1.0 ng mL-1. The platform was applied to detect MAL in lettuce, and the statistical analysis indicated that no significant differences were found between the developed platform and HPLC-MS.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Malation , Reprodutibilidade dos Testes , Aptâmeros de Nucleotídeos/química , DNA/química , DNA de Cadeia Simples , Técnicas Eletroquímicas/métodos
16.
Mol Pharm ; 20(5): 2443-2451, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37067162

RESUMO

Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is a novel radiopharmaceutical based on a novel bidentate inhibitor of FAP that is excreted more slowly than its monomeric counterparts. Still, the efficacy of radiotherapy is mitigated by cascades of DNA damage repair signaling in tumor cells including those via Poly(ADP-ribose) polymerase (PARP). We hereby aimed to evaluate the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in combination with a PARP inhibitor, Olaparib, in the 4T1 murine triple negative breast cancer (TNBC) model. The therapeutic efficacy was visualized using 18F-FDG and [68Ga]Ga-FAPI-04 positron emission imaging/computer tomography (PET/CT). Our results demonstrated that Olaparib suppressed BALB/3T3 fibroblasts in vitro and sensitized the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in mice bearing 4T1 tumors via enhancement of DNA damage. Treatment-associated toxicity was tolerable with only mild leukopenia. Therefore, the combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and Olaparib is a feasible treatment against TNBC.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Gálio/uso terapêutico
17.
Talanta ; 253: 123966, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182706

RESUMO

Organophosphorus pesticides (OPs) are one of the most frequently used pesticides in agriculture, and their residues in environment have caused serious human health and environmental concerns. In this work, we reported a dual-ratiometric electrochemical aptasensor based on carbon nanohorns/anthraquinone-2-carboxylic acid/Au nanoparticles (CNHs/AQ/AuNPs) for simultaneous detection of malathion (MAL) and omethoate (OMT). Here, CNHs/AQ/AuNPs composites were synthesized by a simple room temperature method, and used as a substrate to generate a reference signal (IAQ) and enlarge response signals. Hairpin DNA was then immobilized, offering independent and specific binding sites to further adsorb MB-labelled MAL aptamer (MB-Apt1) and Fc-labelled OMT aptamer (Fc-Apt2). Upon the addition of MAL or OMT, the formation of aptamer-target complex caused the release of MB-Apt1 or Fc-Apt2 from the electrode, resulting in a decrease in IMB or IFc, while IAQ kept unchanged. Based on this principle, the ratiometric signals of IMB/IAQ and IFc/IAQ were used to simultaneously detect MAL and OMT, offering a linear range of 3 pg mL-1 to 3 ng mL-1 for MAL and 10 pg mL-1 to 10 ng mL-1 for OMT, and no significant cross-reactivity existed. By taking advantage of the excellent conductivity and large specific area of CNHs/AQ/AuNPs and the stable two-dimensional structure of hairpin DNA, the aptasensor exhibited high sensitivity, selectivity and reliability. Our work has offered a novel way for simultaneous detection of multiple OPs.


Assuntos
Nanopartículas Metálicas , Praguicidas , Humanos , Malation , Ouro , Compostos Organofosforados , Reprodutibilidade dos Testes , DNA , Carbono
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(4): 469-472, 2022 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-35929168

RESUMO

OBJECTIVE: To ensure the supply of prevention materials in the tertiary public hospitals in prefecturelevel cities, and to make the process of allocating prevention materials more scientific and reasonable. METHODS: Open the green passage, simplify the procurement process, carry out emergency procurement of related materials, ensure timely delivery of prevention materials, distribute them at different levels, and strengthen the warehouse management of prevention materials. RESULTS: The scheme of emergancy supplies was constantly improved, and the supply of prevention materials was completed with good quality. CONCLUSIONS: Using scientific and efficient management methods, the supply of prevention materials in medical institutions has been guaranteed, which has experience and reference significance for the prevention and control of similar public health emergencies in the future.


Assuntos
Emergências , Saúde Pública , Humanos , Centros de Atenção Terciária
19.
EJNMMI Res ; 12(1): 35, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35695985

RESUMO

BACKGROUND: Adnectin is a protein family derived from the 10th type III domain of human fibronectin (10Fn3) with high-affinity targeting capabilities. Positron emission tomography (PET) probes derived from anti-programmed death ligand-1 (PD-L1) Adnectins, including 18F- and 68Ga-labeled BMS-986192, are recently developed for the prediction of patient response to immune checkpoint blockade. The 68Ga-labeled BMS-986192, in particular, is an attractive probe for under-developed regions due to the broader availability of 68Ga. However, the pharmacokinetics and biocompatibility of 68Ga-labeled BMS-986192 are still unknown, especially in non-human primates, impeding its further clinical translation. METHODS: We developed a variant of 68Ga-labeled BMS-986192 using 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) as the radionuclide-chelator. The resultant probe, 68Ga-NODAGA-BMS986192, was evaluated in terms of targeting specificity using a bilateral mouse tumor model inoculated with wild-type B16F10 and B16F10 transduced with human PD-L1 (hPD-L1-B16F10). The dynamic biodistribution and radiation dosimetry of this probe were also investigated in non-human primate cynomolgus. RESULTS: 68Ga-NODAGA-BMS986192 was prepared with a radiochemical purity above 99%. PET imaging with 68Ga-NODAGA-BMS986192 efficiently delineated the hPD-L1-B16F10 tumor at 1 h post-injection. The PD-L1-targeting capability of this probe was further confirmed using in vivo blocking assay and ex vivo biodistribution studies. PET dynamic imaging in both mouse and cynomolgus models revealed a rapid clearance of the probe via the renal route, which corresponded to the low background signals of the PET images. The probe also exhibited a favorable radiation dosimetry profile with a total-body effective dose of 6.34E-03 mSv/MBq in male cynomolgus. CONCLUSIONS: 68Ga-NODAGA-BMS986192 was a feasible and safe tool for the visualization of human PD-L1. Our study also provided valuable information on the potential of targeted PET imaging using Adnectin-based probes.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35627840

RESUMO

Landscape elements have become an important means to improve the quality of life of residents because of their direct influence on the thermal environment, but the selection and configuration of landscape elements have different effects on human thermal comfort in different climate conditions. In this research, the typical residential area of Lhasa in Tibet was taken as the research object, the experimental scheme was prepared using an orthogonal test, and the simulation was carried out using ENVI-met to explore the influences of the green configuration, water area, and ground reflectance, as well as their interaction with the thermal environment in winter and summer under alpine climate conditions. Taking the physiological equivalent temperature (PET) as the optimization index, the optimal design scheme for the synergistic effect of the residential landscape elements was determined. The results were as follows. (1) The order of the landscape configuration factors was as follows: green configuration > water area > leaf area index > ground reflectance in summer. In winter, the order was green configuration > water area > ground reflectance > leaf area index (LAI). (2) With the combined driving of the orthogonal test and the numerical simulation, the optimal scheme of the landscape elements was determined, which was "tree shrub lawn, water area ratio 16%, ground reflectance 0.5, and LAI = 3 m2/m3". (3) Finally, the optimal design strategy of the landscape configuration was proposed for the typical outdoor active space of the Lhasa residential area.


Assuntos
Clima , Qualidade de Vida , Humanos , Estações do Ano , Temperatura , Água
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